scholarly journals Antibacterial Activity of Co(III) Complexes with Diamine Chelate Ligands against a Broad Spectrum of Bacteria with a DNA Interaction Mechanism

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 946
Author(s):  
Katarzyna Turecka ◽  
Agnieszka Chylewska ◽  
Michał Rychłowski ◽  
Joanna Zakrzewska ◽  
Krzysztof Waleron
Keyword(s):  
Electron Microscopy ◽  
Dna Cleavage ◽  
Bacterial Resistance ◽  
Antitumor Agents ◽  
Cell Damage ◽  
Interaction Mechanism ◽  
Spectrophotometric Titration ◽  
Dna Interaction ◽  
Cell Membrane Permeability ◽  
Chelate Ligands

Cobalt coordination complexes are very attractive compounds for their therapeutic uses as antiviral, antibacterial, antifungal, antiparasitic, or antitumor agents. Two Co(III) complexes with diamine chelate ligands ([CoCl2(dap)2]Cl (1) and [CoCl2(en)2]Cl (2)) (where dap = 1,3-diaminopropane, en = ethylenediamine) were synthesized and characterized by elemental analysis, an ATR technique, and a scan method and sequentially tested against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration results revealed that anaerobic and microaerophilic bacteria were found to be the most sensitive; the serial passages assay presented insignificant increases in bacterial resistance to both compounds after 20 passages. The synergy assay showed a significant reduction in the MIC values of nalidixic acid when combined with Compounds (1) or (2). The assessment of cell damage by the complexes was performed using scanning electron microscopy, transmission electron microscopy, and confocal microscopy, which indicated cell membrane permeability, deformation, and altered cell morphology. DNA interaction studies of the Co(III) complexes with plasmid pBR322 using spectrophotometric titration methods revealed that the interaction between Complex (1) or (2) and DNA suggested an electrostatic and intercalative mode of binding, respectively. Furthermore, the DNA cleavage ability of compounds by agarose gel electrophoresis showed nuclease activity for both complexes. The results suggest that the effect of the tested compounds against bacteria can be complex.

scholarly journals Effects of the cationic protein poly-L-arginine on airway epithelial cellsin vitro

2002 ◽  
Vol 11 (3) ◽  
pp. 141-148 ◽  
Author(s):  
Shahida Shahana ◽  
Caroline Kampf ◽  
Godfried M. Roomans
Keyword(s):  
Electron Microscopy ◽  
Epithelial Cells ◽  
Cell Membrane ◽  
Cell Damage ◽  
Membrane Damage ◽  
Light And Electron Microscopy ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Cationic Protein ◽  
Induced Apoptosis

Background: Allergic asthma is associated with an increased number of eosinophils in the airway wall. Eosinophils secrete cationic proteins, particularly major basic protein (MBP).Aim: To investigate the effect of synthetic cationic polypeptides such as poly-L-arginine, which can mimic the effect of MBP, on airway epithelial cells.Methods: Cultured airway epithelial cells were exposed to poly-L-arginine, and effects were determined by light and electron microscopy.Results: Poly-L-arginine induced apoptosis and necrosis. Transmission electron microscopy showed mitochondrial damage and changes in the nucleus. The tight junctions were damaged, as evidenced by penetration of lanthanum. Scanning electron microscopy showed a damaged cell membrane with many pores. Microanalysis showed a significant decrease in the cellular content of magnesium, phosphorus, sodium, potassium and chlorine, and an increase in calcium. Plakoglobin immunoreactivity in the cell membrane was decreased, indicating a decrease in the number of desmosomes.Conclusions: The results point to poly-L-arginine induced membrane damage, resulting in increased permeability, loss of cell-cell contacts and generalized cell damage.

scholarly journals Cu(II) and Ni(II) Complexes with New Tridentate NNS Thiosemicarbazones: Synthesis, Characterisation, DNA Interaction, and Antibacterial Activity

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Dorian Polo-Cerón
Keyword(s):  
Metal Complexes ◽  
Dna Cleavage ◽  
Thermal Analyses ◽  
Dna Interaction ◽  
Antimicrobial Activities ◽  
Tridentate Ligand ◽  
Bacterial Strains ◽  
Azomethine Group ◽  
Broth Microdilution Method

This paper reports the synthesis and detailed characterisation of copper(II) and nickel(II) complexes with tridentate thiosemicarbazone ligands H2L1 and H2L2 derived from 2-acetylpyrazine. The ligands and their metal complexes were characterised by different physicochemical techniques, including elemental and thermogravimetric analysis; UV-Vis, IR, 1H-NMR, and 13C-NMR spectroscopy; molar conductance measurements; and mass spectrometry. The crystal structure of the H2L1 ligand was determined by single crystal X-ray diffraction studies. The spectral data showed that the thiosemicarbazone behaves as an NNS tridentate ligand through the nitrogen atoms of the azomethine group and pyrazine ring and the sulphur atom of the thioamide group. Elemental and thermal analyses indicated that the obtained metal complexes had a 1 : 1 stoichiometry (metal-ligand). The interactions between these complexes and calf thymus DNA (CT-DNA) were studied by electronic absorption and viscosity measurements. The activities of these compounds against oxidative DNA cleavage were examined by agarose gel electrophoresis. Cu(II) and Ni(II) complexes can wind DNA strands through groove interactions and promote strand breakage of the plasmid pmCherry under oxidative stress conditions. Moreover, all the complexes could interact more strongly with DNA than could with the free ligands. Finally, the antibacterial activities of the ligands and their complexes were determined by in vitro tests against Gram-positive bacterial strains (S. aureus ATCC 25923, L. monocytogenes ATCC 19115, and B. cereus ATCC 10876) and Gram-negative bacterial strains (E. coli ATCC 25922, S. typhimurium ATCC 14028, and K. pneumoniae ATCC BAA-2146) using the broth microdilution method. The metal complexes showed greater antimicrobial activities than the precursor ligands against some of the microorganisms.

scholarly journals Ultrastructural Characterization of Proteinuric Patients Predicts Clinical Outcomes

2020 ◽  
Vol 31 (4) ◽  
pp. 841-854 ◽  
Author(s):  
Virginie Royal ◽  
Jarcy Zee ◽  
Qian Liu ◽  
Carmen Avila-Casado ◽  
Abigail R. Smith ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Endothelial Cell ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
Cell Damage ◽  
Digital Pathology ◽  
Ultrastructural Changes ◽  
Consensus Clustering ◽  
Electron Microscopic ◽  
Systematic Analysis

BackgroundThe analysis and reporting of glomerular features ascertained by electron microscopy are limited to few parameters with minimal predictive value, despite some contributions to disease diagnoses.MethodsWe investigated the prognostic value of 12 electron microscopy histologic and ultrastructural changes (descriptors) from the Nephrotic Syndrome Study Network (NEPTUNE) Digital Pathology Scoring System. Study pathologists scored 12 descriptors in NEPTUNE renal biopsies from 242 patients with minimal change disease or FSGS, with duplicate readings to evaluate reproducibility. We performed consensus clustering of patients to identify unique electron microscopy profiles. For both individual descriptors and clusters, we used Cox regression models to assess associations with time from biopsy to proteinuria remission and time to a composite progression outcome (≥40% decline in eGFR, with eGFR<60 ml/min per 1.73 m2, or ESKD), and linear mixed models for longitudinal eGFR measures.ResultsIntrarater and interrater reproducibility was >0.60 for 12 out of 12 and seven out of 12 descriptors, respectively. Individual podocyte descriptors such as effacement and microvillous transformation were associated with complete remission, whereas endothelial cell and glomerular basement membrane abnormalities were associated with progression. We identified six descriptor-based clusters with distinct electron microscopy profiles and clinical outcomes. Patients in a cluster with more prominent foot process effacement and microvillous transformation had the highest rates of complete proteinuria remission, whereas patients in clusters with extensive loss of primary processes and endothelial cell damage had the highest rates of the composite progression outcome.ConclusionsSystematic analysis of electron microscopic findings reveals clusters of findings associated with either proteinuria remission or disease progression.

IV. Influence of Vestibular Stimulation

1980 ◽  
Vol 89 (6_suppl3) ◽  
pp. 25-28 ◽  
Author(s):  
Pamela S. Huber ◽  
Irwin A. Ginsberg ◽  
Michael D. Rudnick
Keyword(s):  
Cell Membrane ◽  
Hair Cell ◽  
Inner Ear ◽  
Membrane Permeability ◽  
Cell Damage ◽  
Dosage Level ◽  
Vestibular Stimulation ◽  
Cell Membrane Permeability ◽  
The Impact ◽  
Inner Ear Fluids

Guinea pigs were given transtympanic dosages of neomycin followed by three hours of either vestibular stimulation or immobilization to test the hypothesis that inner ear hair cell membrane permeability is increased for drugs as a consequence of the transduction process. It was found, however, that neither the topographic pattern nor the degree of hair cell damage differed between the two groups. It is concluded that if the transduction process is accompanied by cell membrane permeability changes, the effect is not an increased susceptibility to neomycin toxicity. A measurable effect of stimulation was the significant decrease in the standard deviation of the mean dosage-damage response at each dosage level. This increase in reliability probably resulted from mixing of the inner ear fluids (especially in the vestibular compartment) which encouraged consistent dosages to the hair cells with each repeated trial. Finally, the impact of these findings on hypotheses related to the mechanism of selective ototoxicity is discussed briefly.

Benzene metabolites antagonize etoposide-stabilized cleavable complexes of DNA topoisomerase IIα

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 830-833 ◽  
Author(s):  
Ronda K. Baker ◽  
Ebba U. Kurz ◽  
David W. Pyatt ◽  
Richard D. Irons ◽  
David J. Kroll
Keyword(s):  
Dna Cleavage ◽  
Acute Myelogenous Leukemia ◽  
Antitumor Agents ◽  
Myelogenous Leukemia ◽  
Topoisomerase Iiα ◽  
Dna Topoisomerase ◽  
Cytogenetic Aberrations ◽  
Acute Myelogenous ◽  
Topo Ii ◽  
Cleavable Complex

Abstract Chronic exposure to benzene is associated with hematotoxicity and acute myelogenous leukemia. Inhibition of topoisomerase IIα (topo II) has been implicated in the development of benzene-induced cytogenetic aberrations. The purpose of this study was to determine the mechanism of topo II inhibition by benzene metabolites. In a DNA cleavage/relaxation assay, topo II was inhibited byp-benzoquinone and hydroquinone at 10 μM and 10 mM, respectively. On peroxidase activation, inhibition was seen with 4,4′-biphenol, hydroquinone, and catechol at 10 μM, 10 μM, and 30 μM, respectively. But, in no case was cleavable complex stabilization observed and the metabolites appeared to act at an earlier step of the enzyme cycle. In support of this conclusion, several metabolites antagonized etoposide-stabilized cleavable complex formation and inhibited topo II–DNA binding. It is therefore unlikely that benzene-induced acute myelogenous leukemia stems from events invoked for leukemogenic topo II cleavable complex-stabilizing antitumor agents.

scholarly journals PC 12 Pheochromocytoma Cell Response to Super High Frequency Terahertz Radiation from Synchrotron Source

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 162 ◽  
Author(s):  
Palalle Perera ◽  
Dominique Appadoo ◽  
Samuel Cheeseman ◽  
Jason Wandiyanto ◽  
Denver Linklater ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cell Membrane ◽  
Electromagnetic Radiation ◽  
High Frequency ◽  
Biological Effects ◽  
Cell Membrane Permeability ◽  
Temporary Increase ◽  
Thz Radiation ◽  
Synchrotron Source ◽  
Pc 12 Cells

High frequency (HF) electromagnetic fields (EMFs) have been widely used in many wireless communication devices, yet within the terahertz (THz) range, their effects on biological systems are poorly understood. In this study, electromagnetic radiation in the range of 0.3–19.5 × 1012 Hz, generated using a synchrotron light source, was used to investigate the response of PC 12 neuron-like pheochromocytoma cells to THz irradiation. The PC 12 cells remained viable and physiologically healthy, as confirmed by a panel of biological assays; however, exposure to THz radiation for 10 min at 25.2 ± 0.4 °C was sufficient to induce a temporary increase in their cell membrane permeability. High-resolution transmission electron microscopy (TEM) confirmed cell membrane permeabilization via visualisation of the translocation of silica nanospheres (d = 23.5 ± 0.2 nm) and their clusters (d = 63 nm) into the PC 12 cells. Analysis of scanning electron microscopy (SEM) micrographs revealed the formation of atypically large (up to 1 µm) blebs on the surface of PC 12 cells when exposed to THz radiation. Long-term analysis showed no substantial differences in metabolic activity between the PC 12 cells exposed to THz radiation and untreated cells; however, a higher population of the THz-treated PC 12 cells responded to the nerve growth factor (NGF) by extending longer neurites (up to 0–20 µm) compared to the untreated PC12 cells (up to 20 µm). These findings present implications for the development of nanoparticle-mediated drug delivery and gene therapy strategies since THz irradiation can promote nanoparticle uptake by cells without causing apoptosis, necrosis or physiological damage, as well as provide a deeper fundamental insight into the biological effects of environmental exposure of cells to electromagnetic radiation of super high frequencies.

scholarly journals Architecture of the Bacteriophage T4 Activator MotA/Promoter DNA Interaction during Sigma Appropriation

2013 ◽  
Vol 288 (38) ◽  
pp. 27607-27618 ◽  
Author(s):  
Meng-Lun Hsieh ◽  
Tamara D. James ◽  
Leslie Knipling ◽  
M. Brett Waddell ◽  
Stephen White ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Dna Cleavage ◽  
Dynamic Equilibrium ◽  
Bacteriophage T4 ◽  
Three Dimensional ◽  
Promoter Sequence ◽  
Dna Interaction ◽  
Physical Models ◽  
Shape Complementarity ◽  
C Terminus

Gene expression can be regulated through factors that direct RNA polymerase to the correct promoter sequence at the correct time. Bacteriophage T4 controls its development in this way using phage proteins that interact with host RNA polymerase. Using a process called σ appropriation, the T4 co-activator AsiA structurally remodels the σ70 subunit of host RNA polymerase, while a T4 activator, MotA, engages the C terminus of σ70 and binds to a DNA promoter element, the MotA box. Structures for the N-terminal (NTD) and C-terminal (CTD) domains of MotA are available, but no structure exists for MotA with or without DNA. We report the first molecular map of the MotA/DNA interaction within the σ-appropriated complex, which we obtained by using the cleaving reagent, iron bromoacetamidobenzyl-EDTA (FeBABE). We conjugated surface-exposed, single cysteines in MotA with FeBABE and performed cleavage reactions in the context of stable transcription complexes. The DNA cleavage sites were analyzed using ICM Molsoft software and three-dimensional physical models of MotANTD, MotACTD, and the DNA to investigate shape complementarity between the protein and the DNA and to position MotA on the DNA. We found that the unusual “double wing” motif present within MotACTD resides in the major groove of the MotA box. In addition, we have used surface plasmon resonance to show that MotA alone is in a very dynamic equilibrium with the MotA element. Our results demonstrate the utility of fine resolution FeBABE mapping to determine the architecture of protein-DNA complexes that have been recalcitrant to traditional structure analyses.

Ultrastructural Changes in the Cochlea of the Guinea Pig after Fast Neutron Irradiation

1994 ◽  
Vol 110 (4) ◽  
pp. 419-427 ◽  
Author(s):  
Ilsa Schwartz ◽  
Chong-Sun Kim ◽  
See-Ok Shin
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Hair Cell ◽  
Neutron Irradiation ◽  
Hair Cells ◽  
Cell Damage ◽  
Outer Hair Cells ◽  
Transmission Electron ◽  
Fast Neutron Irradiation ◽  
Hair Cell Damage

Guinea pigs were irradiated with fast neutrons. After a single dose of 2, 6, 10, or 15 Gy was applied, scanning and transmission electron microscopy of the temporal bone was performed to assess the effect of fast neutron irradiation on the cochlea. Outer hair cell damage appeared with neutron irradiation of more than 10 Gy, and Inner hair cell damage with neutron Irradiation of more than 15 Gy. Outer hair cells were more severely damaged than Inner hair cells. No statistically significant differences were found in damage of basal, middle, and apical turns. The second and third rows of outer hair cells were more severely damaged than the first row of outer hair cells. The most significant findings in transmission electron microscopy were clumping of chromatin and extension of the heterochromatin in the nuclei of hair cells. The cytoplasmic changes were sequestration of cytoplasm, various changes of mitochondria, formation of vacuoles, and irregularly arranged stereocilia. The morphologic change in stria vascularis was intercellular and perivascular fluid accumulation. It appeared to be a reversible process.

scholarly journals DNA Interaction and DNA Cleavage Studies of a New Platinum(II) Complex Containing Aliphatic and Aromatic Dinitrogen Ligands

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Nahid Shahabadi ◽  
Soheila Kashanian ◽  
Maryam Mahdavi ◽  
Noorkaram Sourinejad
Keyword(s):  
Dna Cleavage ◽  
Helical Structure ◽  
Dna Interaction ◽  
Van Der Waals Interactions ◽  
Double Helical Structure ◽  
Intercalative Mode ◽  
Physico Chemical ◽  
Calf Thymus ◽  
Enthalpy And Entropy Changes ◽  
Ct Dna

A new Pt(II) complex, [Pt(DIP)(LL)](NO3)2(in which DIP is 4,7-diphenyl-1,10-phenanthroline and LL is the aliphatic dinitrogen ligand,N,N-dimethyl-trimethylenediamine), was synthesized and characterized using different physico-chemical methods. The interaction of this complex with calf thymus DNA (CT-DNA) was investigated by absorption, emission, circular dichroism (CD), and viscosity measurements. The complex binds to CT-DNA in an intercalative mode. The calculated binding constant,Kb, was  M−1. The enthalpy and entropy changes of the reaction between the complex and CT-DNA showed that the van der Waals interactions and hydrogen bonds are the main forces in the interaction with CT-DNA. In addition, CD study showed that phenanthroline ligand insert between the base pair stack of double helical structure of DNA. It is remarkable that this complex has the ability to cleave the supercoiled plasmid.

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